外泌体糖基化在肿瘤诊断和治疗中的应用进展

doi:10.3969/j.issn.1673-8640.2024.04.016

摘要/Abstract

摘要：

外泌体是细胞通讯的重要媒介，在细胞之间运送RNA、蛋白质和脂质等物质。糖链是外泌体的重要成分。糖基化是蛋白质的重要翻译后修饰，可通过糖基转移酶的作用把糖链转移至蛋白质，丰富了蛋白质的功能和信息含义，可为疾病的诊断和治疗提供新的生物标志物和干预靶标。外泌体与肿瘤母细胞存在一致的异常糖链，其糖基化或可成为循环肿瘤标志物。文章探讨了外泌体糖基化的生理意义、临床价值和治疗应用前景，并介绍了外泌体的捕获技术，这些技术为外泌体糖基化的深入研究提供了方法学支持。外泌体糖基化的研究将为液体活检应用于恶性肿瘤的精确诊断、高危预警和全程精准管理提供新的策略。

关键词: 外泌体, 糖基化, 捕获方法, 肿瘤, 标志物

Abstract:

As an important medium of cellular communication，exosomes transport RNA，proteins and lipids between cells. The glycan structure is an important component of exosomes. Glycosylation，as one of the important ways of protein post-translational modification，enriches the function and information meaning of proteins by transferring glycan structure to proteins under the action of glycosyltransferase and provides new biomarkers and intervention targets for the diagnosis and treatment of diseases. There are abnormal N-glycan structures consistent with tumor cells in the exosomes，and the glycosylation of exosomes may be as a circulating tumor marker. This review focuses on the physiological significance，clinical value and therapeutic prospect of exosomal glycosylation，and it introduces the exosome capture techniques，which provides methodological support for the further study of exosomal glycosylation. The study of exosomal glycosylation will provide a new strategy for the application of liquid biopsy in the accurate diagnosis，high risk warning and accurate management of malignant tumors.

Key words: Exosome, Glycosylation, Capture method, Tumor, Marker

中图分类号:

R446.1

王榕, 高春芳. 外泌体糖基化在肿瘤诊断和治疗中的应用进展[J]. 检验医学, 2024, 39(4): 404-409.

WANG Rong, GAO Chunfang. Application progress of exosomal glycosylation in diagnosis and treatment of tumors[J]. Laboratory Medicine, 2024, 39(4): 404-409.

图/表 2

参考文献 61

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样本类型	生物标志物	疾病	参考文献
尿	四天线聚糖结构	前列腺癌	[27]
尿	凝集素的结合谱	常染色体显性遗传性多囊肾	[22]
尿	两天线结构	半乳糖血症	[28]
尿	富含亮氨酸α2糖蛋白	非小细胞肺癌	[29]
血	蛋白质O-Glc NAC修饰水平	结直肠癌	[30]
血	Α-2-HS-糖蛋白	非小细胞肺癌	[31]
血	触珠蛋白的岩藻糖基化水平	胆管癌	[32]
血	黏蛋白-1	非小细胞肺癌	[33]
腹水	CD24	卵巢癌	[34]
腹水	可溶性半乳糖凝集素3结合蛋白	卵巢癌	[35]
腹水	CD133和糖基化水平	卵巢癌	[36]

样本类型	生物标志物	疾病	参考文献
尿	四天线聚糖结构	前列腺癌	[27]
尿	凝集素的结合谱	常染色体显性遗传性多囊肾	[22]
尿	两天线结构	半乳糖血症	[28]
尿	富含亮氨酸α2糖蛋白	非小细胞肺癌	[29]
血	蛋白质O-Glc NAC修饰水平	结直肠癌	[30]
血	Α-2-HS-糖蛋白	非小细胞肺癌	[31]
血	触珠蛋白的岩藻糖基化水平	胆管癌	[32]
血	黏蛋白-1	非小细胞肺癌	[33]
腹水	CD24	卵巢癌	[34]
腹水	可溶性半乳糖凝集素3结合蛋白	卵巢癌	[35]
腹水	CD133和糖基化水平	卵巢癌	[36]

方法	原理	优点	缺点	纯度	参考文献
超速离心法	大小和密度不同的成分具有不同的沉积速度	适合大批量样本，技术成熟	耗时长，操作繁琐，产量低，容易对外泌体造成机械损伤	中	[55??-58]
过滤法	根据组分的尺寸来分离分子	不需要特殊设备和试剂	过滤膜堵塞，小粒径外泌体损失	高	[42,59]
沉淀法	利用电荷或水化膜使外泌体聚集沉淀	操作简单，适用于大体积样本	易共沉淀非囊泡物质	低	[44]
免疫亲和层析法	将抗体共价连接到固相材料上，利用抗原抗体的特异性结合分离	外泌体亚型分离特异性高	成本高，取决于抗体的特异性	高	[50,60]
凝集素捕获法	外泌体表面丰富的糖链可以和凝集素结合	简便、快速、精准分离，重复性好，分离后的外泌体形态完整	凝集素亲和力不足，组织渗透性差	高	[61]

方法	原理	优点	缺点	纯度	参考文献
超速离心法	大小和密度不同的成分具有不同的沉积速度	适合大批量样本，技术成熟	耗时长，操作繁琐，产量低，容易对外泌体造成机械损伤	中	[55??-58]
过滤法	根据组分的尺寸来分离分子	不需要特殊设备和试剂	过滤膜堵塞，小粒径外泌体损失	高	[42,59]
沉淀法	利用电荷或水化膜使外泌体聚集沉淀	操作简单，适用于大体积样本	易共沉淀非囊泡物质	低	[44]
免疫亲和层析法	将抗体共价连接到固相材料上，利用抗原抗体的特异性结合分离	外泌体亚型分离特异性高	成本高，取决于抗体的特异性	高	[50,60]
凝集素捕获法	外泌体表面丰富的糖链可以和凝集素结合	简便、快速、精准分离，重复性好，分离后的外泌体形态完整	凝集素亲和力不足，组织渗透性差	高	[61]